Hypertension. 1997;30:629-631
(Hypertension. 1997;30:629.)
© 1997 American Heart Association, Inc.
Lipid Metabolism Alterations in Normotensive Subjects With Positive Family History of Hypertension
Heno Ferreira Lopes;
Hélio Bernardes Silva;
José Augusto Soares;
Barreto Filho;
Fernanda Marciano Consolim-Colombo;
Dante Marcelo Artigas Giorgi;
Eduardo Moacyr Krieger
From the Hypertension Unit, Heart Institute, HCFMUSP, São Paulo,
Brazil.
Correspondence to Heno Ferreira Lopes, MD, Hypertension Unit, Heart Institute, Av Dr Eneas de Carvalho Aguiar, 44, 05403-000 São Paulo, Brazil.
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Abstract
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Abstract Metabolic abnormalities are usually
reported in hypertensive
patients. These metabolic
alterations seem to begin in childhood.
The young offspring of
hypertensive parents have not been studied
thoroughly for
metabolic alterations. The aim of this study
was to examine
the level of total cholesterol, LDL
cholesterol,
VLDL cholesterol, HDL
cholesterol, uric acid, glycemia, aldosterone,
and plasma renin activity in a population of 42 young, slender
normotensive subjects with positive family history of hypertension
(FH+) or negative family history of hypertension (FH-). Measurements
were made in 20 young normotensive subjects (age 21.1±2.2
years, 11
males, 15 white, 5 oriental, body mass index of 22.1±2.3
kg/m
2) with FH+ and 22 young normotensive subjects (age
19.9±1.4
years, 17 males, 17 white, 5 oriental, body mass index of
22.1±2.3
kg/m
2) with FH-. The total
cholesterol (4.47±0.8 versus
3.95±0.6 mmol/L), LDL
cholesterol (2.74±0.63
versus 2.36±0.61 mmol/L),
VLDL cholesterol (0.5±0.25
versus 0.35±0.09 mmol/L),
and triglycerides (2.52±1.26
versus 1.76±0.5 mmol/L)
were significantly elevated
(
P<.05) in the FH+ group
compared with the FH- group. The
total cholesterol/HDL
cholesterol ratio was significantly higher
in the group
with a positive family history of hypertension
(3.75±0.02 versus
3.11±0.02,
P<.05). Glycemia
was slightly elevated in the
FH+ group (2.16±0.29 mmol/L)
but was not significantly different
from that of the FH- group
(2±0.2 mmol/L). Uric acid, plasma
renin activity, and
aldosterone were similar in both
groups. We conclude that young,
slender normotensive subjects with a
positive history of hypertension
show alterations in lipid
metabolism, suggesting a positive
correlation between lipid
metabolism and hypertension heredity.
Key Words: hypertension blood pressure lipid metabolism
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Introduction
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Hypertension
is frequently accompanied by metabolic disorders
such as
elevated triglyceride level, low level of HDL
cholesterol,
increase in LDL cholesterol, and
glucose intolerance or insulin
resistance.
1 Borderline
hypertensive subjects when compared
with normotensive subjects have
higher cholesterol level, higher
triglyceride
level, lower HDL cholesterol, and higher insulin
level.
2 DNA familial markers of some lipid abnormalities
or
hypertension have been described before.
3 Lipid
abnormalities
and hypertension independently or occurring together are
important
risk factors to the atherosclerosis process,
and this process
seems to begin early in life, in childhood.
Metabolic and endocrine
abnormalities (elevated total
cholesterol, LDL cholesterol,
low HDL
cholesterol, and elevated norepinephrine,
renin, and
insulin) have been observed more frequently in normotensive
subjects with a family history of hypertension than in subjects
with a
negative family history of hypertension,
4 5 6 resulting
in a
positive correlation between lipid metabolism and
hypertension
heredity. Most of the data involving
metabolism and the genetics
of hypertension were obtained
in adult normotensive subjects
and not in children and postpubertal
subjects, when hypertension
seems to begin. We have previously shown
that postpubertal
normotensives with a positive family history of
hypertension
have an elevated casual systolic blood pressure
and elevated
sustained (1-hour resting period, Finapres, Ohmeda-2300)
systolic,
mean, and diastolic resting blood
pressures, suggesting a permanent
abnormality rather than a momentary
hyperreactivity producing
the increased arterial
pressure.
7 The aim of this study was
to evaluate the
metabolic and humoral profile in young, slender
normotensive subjects with positive and negative histories
of
hypertension.
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Methods
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Subjects
Forty-two healthy normotensive medical students were selected
for the study. They were considered normotensive when casual
blood
pressure measured after 10 minutes of rest in sitting
position at least
two times was <140/90 mm Hg. Arterial
blood pressure
was measured with a mercury sphygmomanometer,
using the disappearance
of Korotkoff sounds (phase V) as the
criterion for the determination of
diastolic blood pressure.
Subjects with obesity were
excluded; degree of obesity was
estimated by determining body mass
index. The parents with
positive or negative history of hypertension
were identified
by finding evidence in their medical records of
antihypertensive
treatment or by direct measurement of parents blood
pressure.
No history of diabetes was detected in the parents. Subjects
were subdivided into two groups according to their parents
blood
pressure status: positive family history (FH+) when one
or two parents
were hypertensive and negative family history
(FH-) when both parents
were normotensive. The age of the population
was limited to 18 to 25
years. The characteristics of the two
groups are presented in
Table 1
, showing that the two groups
were similar in regard to age,
sex, and race. All participants
signed an informed consent approved by
the Ethics Committee
from the Hospital das Clinicas, São
Paulo University.
Protocol
All subjects reported to our laboratory at approximately
8 AM after an overnight fast. After the subjects
rested for 1 hour in a supine position, blood samples were
collected for measurement of total cholesterol, HDL
cholesterol, LDL cholesterol, VLDL
cholesterol, uric acid, triglycerides,
glycemia, plasma renin activity, and aldosterone. Total
cholesterol level was measured by the CHOD-PAP method
and the LDL-cholesterol concentration was calculated indirectly
(Friedewald formula). The HDL cholesterol was separated
with the phosphotungstic acid/magnesium chloride method. Glucose,
triglycerides, and uric acid were measured by the enzymatic
colorimetric test (GPO/PAP method).
Aldosterone and plasma renin activity were measured by
radioimmunoassay.
Statistical Analysis
Statistical analysis was performed with the statistical
software SAS/STAT.8 Comparisons between categorical
variables were performed with the
2 test.
Students nonpaired t test was applied for the comparison
between two related samples. Values for continuous variables are
expressed as mean±SD. A value of P<.05 was the minimal
level of statistical significance.
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Results
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Table 1
shows that the two
groups of youngsters under study
did not differ significantly regarding
age, sex, race, and
body mass index. The mean systolic and
diastolic blood pressures
were significantly higher in the
FH+ than in the FH- group
(Table 1
). Table 2
shows that mean plasma total
cholesterol,
LDL cholesterol, VLDL
cholesterol, and triglycerides were
significantly
higher in normotensive subjects with positive
history of hypertension
than in normotensive subjects without history
of hypertension,
whereas HDL cholesterol did not differ in
either group. In
addition, the ratio of total cholesterol
to HDL cholesterol
was significantly higher in the FH+ than
in the FH- group.
The uric acid level was similar in the FH+
(0.12±0.03
mmol/L) and FH- (0.12±0.03
mmol/L) groups, respectively.
Mean fasting plasma glucose was
slightly elevated in the FH+
group (2.16±0.29 mmol/L) but
was not significantly different
from that of the FH- group
(2±0.2 mmol/L,
P=NS). The
plasma renin activity
was not different in the FH+ and FH-
groups (1.0±1.0 and 1.0±0.9
ng · mL
-1 ·
h
-1, respectively), and
aldosterone levels did not
differ between FH+ and FH-
groups (0.27±0.07 and 0.24±0.09
mmol/L,
respectively).
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Table 2. Plasma Lipid and Glycemia Concentrations in
Normotensive Subjects With Positive and Negative Family Histories of
Hypertension
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Discussion
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Metabolic abnormalities and hypertension are
frequently associated,
and this fact contributes to the development of
cardiovascular
disease. The metabolic
abnormalities seem to develop along
with hypertension early in life in
subjects with genetic predisposition
to hypertension. As we have
observed before, young normotensive
subjects with a positive family
history of hypertension exhibit
a sustained elevated blood pressure;
they seem to reflect not
just a transient blood pressure elevation, but
one representing
a premature and true increase in blood
pressure levels.
7 In
the present study, the young,
lean normotensive subjects with
a positive history of hypertension had
elevated levels of total
cholesterol, LDL
cholesterol, VLDL cholesterol, and
triglycerides
when compared with young, lean normotensives
without a history
of hypertension. The HDL cholesterol
level was not different
in the FH+ and FH- groups. The basal glucose
was slightly elevated
in the FH+ group, but it was not significantly
different. These
characteristics found in normotensive youngsters with
a positive
history of hypertension, associated with other abnormalities
such as insulin resistance and altered glucose tolerance, are
relatively frequent in hypertensive patients.
6 9 Adult
normotensive
patients with a family history of hypertension compared
with
hypertensive patients with or without a family history of
hypertension
have a similar metabolic
profile.
6 Metabolic alterations in
offspring
of hypertensive subjects have been observed before,
5 10 11
but the studies were usually performed in subjects older
than in our
population, and these subjects were exposed for
longer times to
environmental factors, which may interfere
with the
metabolic condition. The metabolic
abnormalities
observed in this study could possibly contribute to
vascular
structural and reactivity modification early in life. Lipid
metabolism alterations are considered risk factors for
coronary
artery disease, and subjects with a positive history
of hypertension
could be more susceptible to hypertension and
cardiovascular
disease. Therefore, this population
deserves special preventive
care. Treatment of hypertension usually
begins during adulthood,
at a time when considerable damage may have
already been done
to the arterial system, the left
ventricle, and perhaps to
other organs.
12 Consequently, it
is convenient to identify
individual children who are at high risk for
cardiovascular
disease, according to family history of
hypertension, presence
of obesity, inactivity, and consumption of
high-fat meat. The
plasma renin activity and aldosterone
level were described
as similar or low in offspring of hypertensive
parents,
13 14 and in our study the values did not differ
between groups.
Also, the uric acid level was similar in both groups.
In conclusion,
young, lean normotensive subjects with a positive
history of
hypertension show alterations in lipid
metabolism, suggesting
a positive correlation between lipid
metabolism and hypertension
heredity.
Received March 17, 1997;
first decision April 30, 1997;
accepted May 19, 1997.
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